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ACETYLCHOLINESTERASE Acetylcholinesterase (AChE - a serine hydrolase) is a closely T3-related chemical found in vertebrate neurons that carries information across the synaptic cleft, the space between two nerve cells. It breaks down unused acetylcholine. This enzyme is necessary to restore the synaptic cleft so it is ready to transmit the next nerve impulse. In the late-1970's many reports came that choline acetyltransferase, the enzyme responsible for the synthesis of acetylcholine, was virtually wiped out in some regions of Alzheimer's disease (AD) patients' brains, and many treatments were started aimed at replacing the missing acetylcholine, but cholinergic replacement therapy ultimately proved disappointing. It has since been shown that there appears to be severely impaired G-protein function and activation by muscarinic receptors of phosphoinositide signaling in AD. The deficit in AD in muscarinic receptor-activated [3H]PI hydrolysis now appears to be associated with dysfunctional activation of the coupled G-protein, Gq/11 (Jope, 1996). In autism, reductions (20-30%) in cortical M1 receptor binding levels that reached significance in parietal inner cortical layers were observed. More extensive reductions (60-75%) in the nicotinic receptor subtype a4b2 were apparent in both cortical areas with all cortical layers reaching In thyroid diseases, acethylcholinesterase has long been known to be regulated by thyroid hormones. Results from rat studies show that thyroid hormones are involved in regulating the muscarinic cholinergic neurotransmission in the striatum (Iriuchijima et al, 1991). Increased muscarinic sensitivity has been associated with hypothyroidism (Overstreet et al, 1988). Choline acetyltransferase (ChAT), a specific marker for cholinergic neurons, was decreased in the prefrontal and visual cortices, the striatum and the superior colliculus and increased in the cerebellum of hypothyroid rats (Virgili et al, 1991). Data indicates that hypothyroidism induces an increased responsiveness of M1AChRs and mGluRs and a rise in the soluble PKC activity that could be available and ready for translocation (Pintor et al, 1996). The effect of hypothyroid state on cerebral cortex resulted in an increase of acethylcholinesterase activity both in young and aged rats and was also reflected in an increase of density of M1-AChRs in the young rats (Salvati et al, 1994). A decrease in adrenoreceptor stimulation has been demonstrated to induce an elevation in receptor density, as is observed in hypothyroidism (Hedberg, 1984). Hypothyroidism also induced an increase in the relative percentage of sphingomyelin in young rats. while in aged rats hypothyroidism induced a decrease of sphingomyelin and glycerophosphocholine and an increase of cholesterol (Salvati et al, 1994). Muscarinic cholinergic receptor activation is mediated by Gq/11 (Jope, 1996; Sawaki et al, 1995). ------------------------------------------- Choline acetyltransferase (ChAT) is regulated by T3. FLUORIDE/acetylcholinesterase (120 related papers) FLUORIDE AND PERTUSSIS (300 references) ACETYLCHOLINE & T3 (49 references) ACETYLCHOLINE & HYPOTHYROIDISM (41 references). ----------------------------- Hedberg A - "Adrenergic receptors. Methods of determination and mechanisms of regulation" Acta Med Scand Suppl 72:7-15 (1983) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=6138938&form=6&db=m&Dopt=r Iriuchijima T, Michimata T, Mizuma H, Murakami M, Yamada M, Mori M - "Hypothyroidism inhibits the formation of inositol phosphate in response to carbachol in the striatum of adult rat" Res Commun Chem Pathol Pharmacol 73(2):173-80 (1991) Jope R - “Cholinergic Muscarinic Receptor Signaling by the Phosphoinositide Signal Transduction System in Alzheimer's Disease“Alzheimer's Disease Review 1:2-14 (1996) Overstreet DH, Russell RW, Crocker AD, Gillin JC, Janowsky DS - "Genetic and pharmacological models of cholinergic supersensitivity and affective disorders" Experientia 44(6):465-72 (1988) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=3288493&form=6&db=m&Dopt=r Perry EK, Lee ML, Martin-Ruiz CM, Court JA, Volsen SG, Merrit J, Folly E, Iversen PE, Bauman ML, Perry RH, Wenk GL - Cholinergic activity in autism: abnormalities in the cerebral cortex and basal forebrain” Am J Psychiatry 2001 Jul;158(7):1058-66 (2001) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=11431227&form=6&db=m&Dopt=r Pintor A, Fortuna S, Lorenzini P, Pascale A, Battaini F, Avellino C, Malvezzi Campeggi L, Salvati S - "Influences of hypothyroidism on lipid composition and inositol lipid-linked receptors responsiveness and protein kinase C (PKC) activity in the cerebral cortex of Lewis rats" Neurochem Res 21(5):541-5 (1996) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=8726960&form=6&db=m&Dopt=r Salvati S, Campeggi LM, Sorcini M, Olivieri A, Di Biase A - "Effect of propylthiouracil-induced hypothyroidism on membranes of adult rat brain" Lipids 28(12):1075-8 (1993) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=8121249&form=6&db=m&Dopt=r Sawaki K, Baum BJ, Roth GS, Ambudkar IS - "Decreased m3-muscarinic and alpha 1-adrenergic receptor stimulation of PIP2 hydrolysis in parotid gland membranes from aged rats: defect in activation of G alpha q/11" Arch Biochem Biophys 322(2):319-26 (1995) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=7574703&form=6&db=m&Dopt=r Tominaga M, Wada M, Masu M - "Potentiation of capsaicin receptor activity by metabotropic ATP receptors as a possible mechanism for ATP-evoked pain and hyperalgesia" Proc Natl Acad Sci U S A 98(12):6951-6 (2001) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=11371611&form=6&db=m&Dopt=r
Virgili M, Saverino O, Vaccari M, Barnabei O, Contestabile A - "Temporal, regional and cellular selectivity of neonatal alteration of the thyroid state on neurochemical maturation in the rat" Exp Brain Res 1991;83(3):555-61 (1991) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=1851100&form=6&db=m&Dopt=r muscarinic acetylcholine receptor: http://www.graylab.ac.uk/cgi-bin/omd?query=muscarinic&action=Search+OMD Skau KA, Shipley MT - ”Phenylmethylsulfonyl fluoride inhibitory effects on acetylcholinesterase of brain and muscle.” Neuropharmacology 38(5):691-8 (1999) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=10340306&form=6&db=m&Dopt=r
Zhao XL, Wu JH - “Actions of sodium fluoride on acetylcholinesterase activities in rats.” Biomed Environ Sci 11(1):1-6 (1998) Kambam JR, Parris WC, Naukam RJ, Franks JJ, Sastry BV - In vitro effects of fluoride and bromide on pseudocholinesterase and acetylcholinesterase activities.”Can J Anaesth 7(8):916-9 (1990)
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